Clinical Research
Atrial Fibrillation
Efficacy and Safety of Dabigatran Etexilate and Warfarin in “Real-World” Patients With Atrial Fibrillation: A Prospective Nationwide Cohort Study

https://doi.org/10.1016/j.jacc.2013.03.020Get rights and content
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Objectives

The aim of this study was to assess the efficacy and safety in an “everyday clinical practice” population of anticoagulant-naïve patients with atrial fibrillation (AF) treated with dabigatran etexilate after its post-approval availability in Denmark, compared with warfarin.

Background

Concerns have been raised about an excess of bleeding events or myocardial infarction (MI) among patients treated with the new oral direct thrombin inhibitor, dabigatran etexilate.

Methods

From the Danish Registry of Medicinal Product Statistics, we identified a dabigatran-treated group and a 1:2 propensity-matched warfarin-treated group of 4,978 and 8,936, respectively. Comparisons on efficacy and safety outcomes were made on the basis of Cox-proportional hazards models stratified on propensity-matched groups.

Results

Stroke and systemic embolism were not significantly different between warfarin- and dabigatran-treated patients. Adjusted mortality was significantly lower with both dabigatran doses (110 mg b.i.d., propensity-match group stratified hazard ratio [aHR]: 0.79, 95% confidence interval [CI]: 0.65 to 0.95; 150 mg b.i.d., aHR: 0.57, 95% CI: 0.40 to 0.80), when compared with warfarin. Pulmonary embolism was lower compared with warfarin for both doses of dabigatran. Less intracranial bleeding was seen with both dabigatran doses (110 mg b.i.d., aHR: 0.24, 95% CI: 0.08 to 0.56; 150 mg b.i.d., aHR: 0.08, 95% CI: 0.01 to 0.40). The incidence of MI was lower with both dabigatran doses (110 mg b.i.d., aHR: 0.30, 95% CI: 0.18 to 0.49; 150 mg b.i.d., aHR: 0.40, 95% CI: 0.21 to 0.70). Gastrointestinal bleeding was lower with dabigatran 110 mg b.i.d. (aHR: 0.60, 95% CI: 0.37 to 0.93) compared with warfarin but not dabigatran 150 mg b.i.d. The main findings were broadly consistent in a subgroup analysis of dabigatran users with ≥1-year follow-up (median follow-up 13.9 months [interquartile range: 12.6 to 15.3 months]).

Conclusions

In this “everyday clinical practice” post-approval nationwide clinical cohort, there were similar stroke/systemic embolism and major bleeding rates with dabigatran (both doses) compared with warfarin. Mortality, intracranial bleeding, pulmonary embolism, and MI were lower with dabigatran, compared with warfarin. We found no evidence of an excess of bleeding events or MI among dabigatran-treated patients in this propensity-matched comparison against warfarin, even in the subgroup with ≥1-year follow-up.

Key Words

atrial fibrillation
dabigatran
oral anticoagulation
stroke

Abbreviations and Acronyms

aHR
propensity match group stratified hazard ratio
AF
atrial fibrillation
CI
confidence interval
HR
hazard ratio
ICD
International Classification of Diseases
MI
myocardial infarction
OAC
oral anticoagulation
PE
pulmonary embolism
TTR
time in therapeutic range

Cited by (0)

This study was conducted fully independent of any industry or other grant support. The views expressed in this article are the personal views of the authors and do not necessarily represent the position of the Danish Health and Medicines Authority. Dr. Lip has served as a consultant for Bayer, Astellas, Merck, AstraZeneca, Sanofi, BMS/Pfizer, Daiichi-Sankyo, Biotronik, and Boehringer-Ingelheim; and has been on the Speakers’ Bureaus for Bayer, BMS/Pfizer, Boehringer-Ingelheim, and Sanofi. Drs. Larsen and Rasmussen have been on the speakers’ bureaus for Bayer, BMS/Pfizer, Roche Diagnostics, and Boehringer-Ingelheim. Dr. Callréus and Ms. Rosenzweig are full-time employees of the Danish Health and Medicines Authority. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.